Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine.
OBJECTIVE
To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine.


METHODS
Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function.


RESULTS
Application of 1 micromol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of (3)H-mannitol and (14)C-inulin.


CONCLUSIONS
This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.
Moeser
Adam-J
AJ
North Carolina State University, Raleigh NC 27606, USA.
Nighot
Prashant-K
PK
Roerig
Birgit
B
Ueno
Ryuji
R
Blikslager
Anthony-T
AT
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D065101:Chloride Channel Agonists; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D007082:Ileum / Q000098:blood supply*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007444:Inulin / Q000378:metabolism; D054368:Laxatives / Q000494:pharmacology*; D000068238:Lubiprostone; D008297:Male; D008353:Mannitol / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D013552:Swine
D065101:Chloride Channel Agonists; D054368:Laxatives; D008353:Mannitol; D011092:Polyethylene Glycols; D000068238:Lubiprostone; D007444:Inulin; D000527:Alprostadil